Beneficial effects of Huaiqihuang on hyperglycemia-induced MPC5 podocyte dysfunction through the suppression of mitochondrial dysfunction and endoplasmic reticulum stress

Abstract

The present study was performed to investigate the effect of Huaiqihuang (HQH) on hyperglycemia (HG)-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress in MPC5 podocytes. The effects of HQH and HG on cell viability were assessed using an MTT assay. mRNA and protein expression levels were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, whereas reactive oxygen species production and alterations in mitochondrial membrane potential were assessed using flow cytometry. DNA damage was evaluated using a comet assay. The results demonstrated that treatment of podocytes with HQH markedly suppressed the HG‑induced generation of reactive oxygen species. HQH also significantly improved mitochondrial membrane potential in podocytes exposed to HG. When the podocytes were treated with HG, Ca2+ levels were significantly increased, compared with those in the control group, whereas treatment of the podocytes with HQH significantly reversed the HG‑induced upregulation of Ca2+ secretion. Treatment of the podocytes with HQH significantly reversed the HG‑induced upregulation of glucose‑related protein 78 (GRP78) and C/EBP‑homologous protein, which were used as indicators of ER stress. Furthermore, GRP78 loss‑of‑function attenuated HG‑induced podocyte dysfunction, including cell apoptosis and DNA damage. In conclusion, beneficial effects of HQH on HG‑induced MPC5 podocyte dysfunction were observed, and occurred through the suppression of mitochondrial dysfunction and ER stress.

The Effect of Chinese Traditional Medicine Huaiqihuang (HQH) on the Protection of Nephropathy

“…When MPC5 podocytes were cultured in a high glucose medium, intracellular Ca2+ and ROS levels increased significantly, leading to mitochondrial dysfunction. Li et al [12] showed that Huaier can improve the mitochondrial membrane 2…”

“…It also has the ability to inhibit inflammatory cytokine expression like IL-6 and macrophage infiltration [11]. The oxidative stress levels are suppressed with decreased Ca 2+ and ROS expression in podocyte [12]. By means of autophagy, HQH balances the activity between mTOR and HQH [12,13].…”

“…The oxidative stress levels are suppressed with decreased Ca 2+ and ROS expression in podocyte [12]. By means of autophagy, HQH balances the activity between mTOR and HQH [12,13]. HQH can also inhibit the apoptotic p-ERK/CHOP signaling pathway and regulate the Bcl-2/Bax signaling pathway to protect renal intrinsic cells [12].…”

“…By means of autophagy, HQH balances the activity between mTOR and HQH [12,13]. HQH can also inhibit the apoptotic p-ERK/CHOP signaling pathway and regulate the Bcl-2/Bax signaling pathway to protect renal intrinsic cells [12]. Li et al reported that Huaiqihuang can effectively reduce proteinuria in patients with IgAN and significantly reduce hematuria [14].…”

“…The evaluations of serum renal function parameters have proved HQH almost has no cytotoxicity to normal kidney. All the researches show that HQH is likely to become an adjuvant drug for kidney diseases [11,12,15].…”